¶ Clostridium Butyricum for Motor and Non-motor Symptoms in Parkinson's Disease
| Field |
Value |
| NCT Number |
NCT06548256 |
| Status |
Recruiting |
| Sponsor |
Pusan National University (Korea) |
| Phase |
Not specified |
| Intervention |
Miyarisan-BM (Clostridium Butyricum Miyairi) |
Clostridium butyricum is a butyrate-producing gut bacterium that has been studied for its beneficial effects on gut health and inflammation. The proposed mechanisms in Parkinson's disease include:
- Butyrate production: Produces butyrate, a short-chain fatty acid with anti-inflammatory properties
- Gut barrier integrity: Strengthens the intestinal epithelial barrier, reducing leaky gut
- Modulation of gut microbiome: Promotes beneficial bacteria and reduces pathogenic species
- Immune modulation: Reduces systemic inflammation through regulatory T-cell activation
- Gut-brain axis: May influence brain function through vagal nerve signaling and systemic inflammation reduction
The gut-brain axis plays a critical role in Parkinson's disease pathogenesis. Many PD patients exhibit gut dysfunction years before motor symptoms appear. Gut inflammation and dysbiosis may contribute to alpha-synuclein aggregation in the enteric nervous system, which then propagates to the central nervous system via the vagus nerve.
Clostridium butyricum supplementation represents a targeted approach to:
- Reduce gut inflammation
- Restore microbiome balance
- Improve gut barrier function
- Potentially slow alpha-synuclein propagation
¶ Butyrate and Neurodegeneration
Butyrate is a four-carbon short-chain fatty acid (SCFA) produced by bacterial fermentation of dietary fiber in the colon. It serves as:
- Primary energy source for colonocytes
- Histone deacetylase (HDAC) inhibitor: Epigenetic regulation of gene expression
- Anti-inflammatory agent: Modulates immune cell function
- Barrier enhancer: Strengthens gut tight junctions
The mechanisms by which butyrate may influence neurodegenerative processes include:
- HDAC inhibition: Increases histone acetylation, promoting expression of neurotrophic factors (BDNF, GDNF)
- Anti-inflammatory effects: Reduces microglial activation and pro-inflammatory cytokine production
- Mitochondrial function: Improves mitochondrial biogenesis and energy metabolism
- Alpha-synuclein modulation: May reduce aggregation through epigenetic mechanisms
Multiple preclinical studies support the use of butyrate-producing bacteria in PD models:
- Motor function improvement: Reducedrotarod latency in mouse PD models
- Neuroprotection: Preserved dopaminergic neurons in the substantia nigra
- Gut barrier improvement: Restored intestinal epithelial integrity
- Microbiome restoration: Rebalanced gut bacterial populations
- Reduced fecal butyrate levels in PD patients compared to controls
- Correlation between butyrate-producing bacteria and motor symptoms
- Pilot studies showing probiotic benefits on motor scores
- Motor assessment: Change in MDS-UPDRS Part III (motor) score
- Non-motor assessment: Non-Motor Symptoms Scale (NMSS)
- Quality of life: PDQ-39
- Gut microbiome: Changes in fecal bacterial composition
- Inflammatory markers: Serum cytokines
- Butyrate levels: Fecal SCFA concentrations
- Safety: Adverse event monitoring
| Probiotic |
Mechanism |
Evidence |
Stage |
| Clostridium butyricum |
Butyrate production |
Preclinical |
Phase 2 |
| Bacillus subtilis |
Protease, butyrate |
Preclinical |
Phase 2 |
| Lactobacillus |
Various |
Mixed |
Phase 2/3 |
| Multi-strain |
Synergistic |
Moderate |
Phase 3 |
Future studies may explore:
- Synbiotic combinations: Prebiotic + probiotic
- Fecal microbiota transplantation (FMT)
- Targeted metabolic therapy: Direct SCFA supplementation
- Microbiome signatures: Predict treatment response
- Metabolic markers: Monitor butyrate production
- Inflammatory biomarkers: Track anti-inflammatory effects